A back‐of‐the‐envelope risk assessment of star wars

The risks associated with the deployment of a Star Wars system and from a space‐based conflict have been rapidly evaluated on the basis of known facts about SDI‐like programmes. Back‐of‐the‐envelope evaluations indicate that effects of a space‐based conflict might be lethal for life on Earth.     

Chromatin‐ and temperature‐dependent modulation of radiation‐induced double‐strand breaks

Purpose: To investigate the influence of chromatin organization and scavenging capacity in relation to irradiation temperature on the induction of double‐strand breaks (DSB) in structures derived from human diploid fibroblasts.

Materials and methods: Agarose plugs with different chromatin structures (intact cells±wortmannin, permeabilized cells with condensed chromatin, nucleoids and DNA) were prepared and irradiated with X‐rays at 2 or 37°C and lysed using two different lysis protocols (new ice‐cold lysis or standard lysis at 37°C). Induction of DSB was determined by constant‐field gel electrophoresis.

Results: The dose‐modifying factor (DMF_temp) for irradiation at 37 compared with 2°C was 0.92 in intact cells (i.e. more DSB induced at 2°C), but gradually increased to 1.5 in permeabilized cells, 2.2 in nucleoids and 2.6 in naked DNA, suggesting a role of chromatin organization for temperature modulation of DNA damage. In addition, DMF_temp was influenced by the presence of 0.1?M DMSO or 30?mM glutathione, but not by post‐irradiation temperature.

Conclusion: The protective effect of low temperature was correlated to the indirect effects of ionizing radiation and was not dependent on post‐irradiation temperature. Reasons for a dose modifying factor <1 in intact cells are discussed.     

The Biology of non‐violence

This article reviews the examination of aggression in ethology. It concludes that though ethology establishes a biology of aggression, it does not conclude a biological determinism behind human violence. The article begins by examining this miscomprehension. Ethology shows a strong evolutionary tendency for aggression to be non‐violent behaviour. The human, as a higher order social animal, should conform to this. That we do not behave in this way is not a reflection of biology but that of the unique influence of culture on behaviour. Humans tend to non‐violence, biologically; it is culture that alters that tendency. How this is achieved is examined in the latter part of the article. In conclusion, ethologists, from Lorenz onwards, have argued that while aggression is rooted in human biology, violence is not, but has a cultural root. What culture has developed, it can alter, a positive optimistic message from ethology which is too often overlooked.     

Survival with pain: An eight‐year follow‐up of war‐wounded refugees

The aim of this study was to investigate the nature of chronic pain in male war‐wounded refugees and to examine the relationship between chronic pain and psychiatric symptoms. A culturally heterogeneous group of 44 war‐wounded refugees were investigated during hospitalization, shortly after arrival, and followed up after two years. This study is an additional follow‐up after eight years. The data collection methods used were structured interviews and physical examination. The measures of outcome were: Visual Analogue Scale (VAS) grading of pain; clinical categorization of pain into nociceptive or neurogenic; Hopkins Symptom Check List (HSCL‐25); Post Traumatic Symptom Scale (PTSS‐10). Chronic pain was found in 32 (73%) out of 44 subjects. The pain was purely nociceptive and neurogenic in 53% and 25%, respectively. The frequency of psychiatric symptoms was significantly related to the mean intensity of pain. War‐wounded refugees display psychiatric symptoms and chronic pain in a complex pattern. Further research is needed as a basis for pain rehabilitation programmes suitable for this group.     

Therapeutic potential of 5‐[125I]iodo‐2′‐deoxyuridine and methotrexate in the treatment of advanced neoplastic meningitis

Purpose: To assess the therapeutic potential of methotrexate (MTX) and 5‐[¹²⁵I]iodo‐2′‐deoxyuridine (¹²⁵IdUrd) administered sequentially in rats bearing advanced (ten‐day‐old) intrathecal (i.t.) TE671 human rhabdomyosarcoma tumours.

Materials and methods: Nude rats were injected with TE671 cells through an i.t. placed catheter. Ten days later, the animals were injected i.t. over a 12‐day period with (i) saline daily, (ii) MTX every other day, (iii) ¹²⁵IdUrd every other day, or (iv) MTX and ¹²⁵IdUrd on alternating days. Onset of paralysis was determined as a function of time, and the medians for onset (M), percentage of cells killed (% kill), and log cell kill were calculated.

Results: The data show that (i) injection of MTX leads to a moderate delay in the onset of paralysis (M_MTX=29?d versus M_saline=20?d), (ii) administration of ¹²⁵IdUrd is more effective (M_IdUrd=36?d), and (iii) sequential administration of MTX–¹²⁵IdUrd further increases the therapeutic efficacy of ¹²⁵IdUrd (M_MTX–IdUrd=47?d).

Conclusions: Intrathecal injection of MTX–¹²⁵IdUrd is efficacious in the therapy of advanced intrathecal tumours.     

Decomposition of 2‐deoxy‐D‐ribose by irradiation with 0.6 keV electrons and by 0.5 keV ultrasoft X‐rays

Purpose: To compare the molecular decomposition of 2‐deoxy‐D‐ribose induced by 0.6?keV electron irradiation or by 0.5?keV ultrasoft X‐ray irradiation.

Materials and methods: A thin film of 2‐deoxy‐D‐ribose was irradiated by two radiation sources: low‐energy (～0.6?keV) electrons and ultrasoft X‐rays (～0.5?keV). The positive ions that were desorbed from the sample during the irradiation were measured using a quadrupole mass spectrometer. The spectral changes in the X‐ray absorption near edge structure (XANES) were also examined after the irradiation.

Results and discussion: The ions that were desorbed from 2‐deoxy‐D‐ribose due to electron irradiation were mainly H⁺, CH_x⁺, C₂H_x⁺, CO⁺, CH_xO⁺, C₃H_x⁺, C₂H_xO⁺ and C₃H_xO⁺ (x=1, 2, and 3) ions. These ions were the same as those observed in desorption due to ultrasoft X‐ray irradiation. The XANES spectral changes induced by electron irradiation showed C‐O bond cleavage in the molecule and C=O bond formation in the surface residues. These results show that intensive molecular decomposition of the furanose ring structure was induced by both types of irradiation. It is inferred that these irradiation products are primarily produced by secondary electrons (several tens of eV), which are thought to be generated by both types of irradiation when they are applied to the 2‐deoxy‐D‐ribose sample.     

Decreased c‐Myc expression and its involvement in X‐ray‐induced apoptotic cell death of human T‐cell leukaemia cell line MOLT‐4

Purpose: To investigate the possible involvement of c‐Myc and ceramide‐c‐Jun N‐terminal kinase (JNK) pathway in X‐ray‐induced apoptotic cell death of MOLT‐4 cells.

Materials and methods: The expressions of c‐Myc protein and c‐myc mRNA after X‐irradiation were analysed by Western blotting and RT‐PCR between radiosensitive MOLT‐4 and radioresistant variant Rh‐1a cells with less JNK activation than the parental cells. Apoptotic cell death was determined by a dye exclusion test, the appearance of chromatin condensation and DNA fragmentation. The effect of a JNK activator anisomycin or c‐Myc inhibitor peptides (Int‐H1‐S6A, F8A) on the amount of c‐Myc protein and on the induction of apoptosis was investigated, respectively.

Results: In X‐irradiated MOLT‐4 cells, amounts of both c‐myc mRNA and c‐Myc protein rapidly decreased, which was followed by apoptotic cell death, while little change or limited reduction of c‐Myc protein was observed in X‐irradiated Rh‐1a cells with accompanying higher cell viability. Exposure of MOLT‐4 and Rh‐1a cells to c‐Myc inhibitor peptides similarly induced apoptotic cell death with decreases of c‐Myc protein. Anisomycin rapidly induced JNK activation and a subsequent decrease of c‐Myc protein, causing cell death in MOLT‐4 cells. On the other hand, Rh‐1a cells were more resistant to anisomycin than parental MOLT‐4 cells, showing less JNK activation and a delayed decrease of c‐Myc protein.

Conclusion: A decrease of c‐Myc protein was considered important in X‐ray‐induced apoptotic cell death of MOLT‐4 cells; activation of the JNK pathway caused reduction in the amounts of c‐myc mRNA and c‐Myc protein, and finally induced apoptotic cell death.     

Low‐energy Auger‐ and Photo‐electron Effects on the Degradation of Thymine by Ultrasoft X‐irradiation

Purpose: To investigate quantitatively and qualitatively the production of thymine radicals produced by monochromatic ultrasoft X (USX) ‐ or ⁶⁰Co γ‐rays using electron paramagnetic resonance (EPR) spectroscopy.

Materials and Methods: Thymine was chosen as the DNA component for the irradiation. The EPR experiments of irradiated thymine were performed using an X‐band EPR device installed in a soft X‐ray beamline (BL23SU) in SPring‐8. Sample pellets were irradiated with USX photons in a microwave cavity in a vacuum chamber. EPR measurements of thymine powder pellets irradiated with USX photons at energies of 407 and 538?eV were performed at 77?K or room temperature. For reference, ⁶⁰Co γ‐irradiation to a pellet was also performed at room temperature.

Results: The following three features were found: 1) comparison between the two energies shows that the EPR dose‐response curves are clearly distinguishable from each other: the curve for 407?eV saturated at a lower dose and spin number than that for 538?eV. 2) no evident qualitative difference between the radical species produced at the two energies was observed. 3) the EPR signal of the 538?eV USX‐irradiated sample measured after annealing for 12 days is similar to that obtained with ⁶⁰Co γ‐irradiation.

Conclusions: The difference observed in the EPR dose‐response relationship reflects the difference in the K‐absorption cross‐sections of carbon, nitrogen and oxygen in the thymine molecule which govern the photo‐/Auger electron energy spectrum.     

Assessment of DNA damage produced by 125I‐triplex‐forming oligonucleotides in cells

Purpose: Triplex‐forming oligodeoxyribonucleotides (TFOs) bind specifically to their target sequences by forming hydrogen bonds within the major groove of the target duplex. When labeled with Auger‐electron‐emitting radioisotopes, TFOs are able to damage the target gene in a process named antigene radiotherapy. We compared radiotoxicity and the amount of DNA damage produced within cultured cells by two ¹²⁵I‐labeled TFOs, one with a single target in the genome and another with multiple targets.

Materials and methods: Radiotoxicity was measured by clonogenic assay while DNA damage was assessed by the number of histone γ‐H2AX foci formed at the sites of DNA double strand breaks (DSBs).

Results: The TFO with multiple nuclear targets was 1.7 fold more radiotoxic and produced on average 1.9 fold more γ‐H2AX foci per cell than the TFO with a single target.

Conclusion: Since the two methods gave comparable results, measuring the number of γ‐H2AX foci per decay may be a useful procedure for the assessment of cytotoxic effects and the intranuclear localization of radionuclides when they produce DSBs.     

‘In‐field’ and ‘out‐of‐field’ functional impairment during subacute and chronic phases of experimental radiation enteropathy in the rat

Purpose: To investigate subacute and chronic functional consequences of localized irradiation of rat small intestine on exposed and shielded segments (proximal and distal).

Materials and methods: The surgical model of a scrotal hernia was used. The ileal loop was exposed to single doses of 18, 21 or 29.6?Gy X‐irradiation. Epithelial structure and transport capacity were followed 2 and 26 weeks post‐exposure.

Results: Irradiated segments showed mucosal ulceration followed by transmural fibrosis. Transport capacity was impaired from 2 to 26 weeks. Subacute functional impairment was noticed in the proximal segment, without either morphological alteration or neutrophil influx. At 26 weeks, both proximal and distal segments showed impaired epithelial transport capacity, with neutrophil influx in the submucosa in cases of 21‐Gy exposure and in the submucosa and muscularis propria after 29.6?Gy.

Conclusions: Radiation enteritis was characterized by functional impairment, within as well as outside, the irradiation field. During the subacute phase, the irradiated segment may be a source of mediators which might influence intestinal function outside the site of injury via the blood stream and/or enteric nervous system. The development of an intestinal occlusion syndrome during the chronic phase might be responsible for intestinal dysfunction but it does not rule out a possible inflammatory process developing in the shielded parts of the small intestine.     

A response to the critique of regulation of mail‐order pharmacy

Aids law in a nutshell. Jarvis, R.M., Closen, M.L., Hermann, D.H.J., &; Leonard, A.S. (West Publishing Co., St. Paul, Minnesota, 1991), 347 pages, $14.95.     

Low‐dose radiotherapy (LD‐RT) and the modulation of iNOS expression in adjuvant‐induced arthritis in rats

Purpose: Low‐dose radiotherapy (LD‐RT) of arthritic joints applied during the peak of the acute inflammatory response improves the clinical and histomorphological development of adjuvant arthritis. The study was undertaken to investigate the cellular composition of the inflammatory infiltrate and the expression of the pro‐inflammatory and anti‐inflammatory enzymes, inducible nitric oxide synthase (iNOS), cyclo‐oxygenase 2 (COX‐2) and haem‐oxygenase 1 (HO‐1), in response to LD‐RT.

Materials and methods: Adjuvant arthritis in female Lewis rats was induced by intradermal injection of heat‐inactivated mycobacterium tuberculosis on day 0. Both arthritic hind paws were sham irradiated (group 1) or X‐irradiated with either 5×1.0?Gy (group 2) or 5×0.5?Gy (group 3) from days 15 to 19 after induction (15 animals/group). On days 21 (n=12 joints/group) and 30 (n=18 joints/group), cryostat sections were analysed histologically and immunohistologically after specific staining for macrophages, iNOS, COX‐2 and HO‐1.

Results: A total of 5×1.0?Gy or 5×0.5?Gy led to a significant reduction of clinical symptoms from days 21 to 29, and a highly significant reduction of cartilage and bone destruction on day 30. Macrophage‐positive areas could be detected continuously throughout the periarticular infiltrate, and were slightly reduced after LD‐RT on days 21 and 30. This reduction was more pronounced after 5×1.0?Gy. Following LD‐RT, the iNOS score was reduced by about 45–50% on days 21 (p<0.05) and 30 (p<0.001). In contrast, the HO‐1 score was increased by about 50% on days 21 (p=0.08) and 30 (p=0.03).

Conclusions: The clinically and histologically observed prevention of the pro‐gression of adjuvant arthritis after LD‐RT given during the peak of the acute inflam‐matory response and the reduction of cartilage and bone destruction in the chronic phase appears to be related to the modulation of iNOS activity by low X‐ray doses.     

Androgen and the blocking of radiation‐induced sensitization to Fas‐mediated apoptosis through c‐jun induction in prostate cancer cells

Purpose: To clarify the key mechanism by which androgen makes prostate cancer cells highly resistant to Fas‐mediated apoptosis.

Materials and methods: The role of c‐jun induction by 10?nM dihydrotestosterone (DHT) in 5?Gy radiation‐induced up‐regulation of Fas and sensitization to the apoptosis was studied by using the human prostate cancer cell line LNCaP.

Results: On exposure to 5?Gy radiation, LNCaP cells demonstrated high sensitization to Fas‐mediated apoptosis through increased Fas expression, stabilized p53 expression and binding to p53 response elements within the promoter and first intronic region of the Fas gene. Following treatment with DHT, in vivo binding of p53 to its response elements was strongly inhibited. In addition, DHT significantly up‐regulated c‐jun expression through extracellular stress‐regulated kinase (ERK) activation, and transfection of an antisense oligonucleotide for c‐jun or ERK inhibition by PD98059 cancelled DHT‐mediated suppression of radiation‐induced transactivation of Fas gene and sensitization to Fas‐mediated apoptosis.

Conclusions: Radiation‐induced Fas sensitization in prostate cancer cell was mediated through p53‐dependent transactivation of the Fas gene, which can be blocked by androgen stimulation mainly through induction of c‐jun.     

Molecular Simulation of Ligand‐Binding with DNA: Implications for 125I‐Labeled Pharmaceutical Design

Purpose: By using computer‐assisted molecular modeling software, to assess the effects of structural modification on the interaction of ¹²⁵I‐labeled iodoHoechst ligands and DNA and to design new analogs with specified distances between the Auger‐electron‐emitting ¹²⁵I atom and the DNA central axis.

Materials and methods: The Lamarckian genetic algorithm (AutoDock 3.0) was used to model the interaction between DNA and m‐iodo‐p‐methoxyHoechst (IMH), a ligand whose binding to the minor groove of DNA has been demonstrated (crystal structure) and which is available in the Protein Data Bank. m‐Iodo‐p‐ethoxyHoechst (IEH), a radioligand we had previously synthesized and characterized, was then docked onto DNA, the IEH–DNA complex minimized, and the binding free energy and inhibition constant (K_i) estimated and compared with those for IMH–DNA. Using the protocol, several novel iodoHoechst analogs (IH‐A and IH‐B) were designed. Finally, Insight II was used to measure the distances between the iodine atom (e.g. ¹²⁵I) of these Hoechst analogs and of 5‐iodo‐2′‐deoxyuridine (IdUrd) and the central axis of the targeted DNA, and these values were correlated with the expected/measured DSB yield following ¹²⁵I decay.

Results: The docking of IMH and DNA leads to a ligand–DNA complex approximately 1?Å RMSD (root mean square deviation) from the crystal‐structure position, and the IEH–DNA complex also has a small RMSD (1.27?Å). The distances between the ¹²⁵I atom and the DNA central axis are estimated as 8.61?Å for IMH, 9.20?Å for IEH and 5.7?Å for IdUrd. For the newly designed analogs, the distances from the ¹²⁵I atom to the central DNA axis are 10.92?Å for IH‐A and 16.39?Å for IH‐B.

Conclusion: These software programs can predict the reactivity of newly designed radiolabelled molecules with their targeted DNA molecules by molecular modeling prior to their chemical synthesis.     

Persistence of altered 5‐hydroxytryptamine turnover following hemibody X‐irradiation in the rat distal colon

Purpose: Acute gastrointestinal responses to ionizing radiation exposure include a role for 5‐hydroxytryptamine (5‐HT), but it is not known whether involvement of 5‐HT persists and contributes to late effects. The aim was to investigate the acute and later effects of lower hemibody irradiation on 5‐HT turnover and the biological effect in the rat distal colon.

Materials and methods: Rats were exposed to 10?Gy lower hemibody X‐radiation. 5‐HT and 5‐hydroxyindole acetic acid tissue levels were measured in the distal colon along with the serotonin re‐uptake transporter and tryptophan hydroxylase mRNA. 5‐HT‐containing cells and crypt cell numbers were estimated in addition to 5‐HT‐stimulated short‐circuit current responses in isolated mucosa. Studies were performed from 3 days to 3 months post‐exposure.

Results: During the acute phase, at 3 days post‐irradiation, reductions in cell number, tissue resistance, serotonin re‐uptake transporter expression and secretory responses to 5‐HT were observed. However, at later times when secretory responses were normal, 5‐HT tissue levels and enterochromaffin cell numbers were increased.

Conclusions: The results provide evidence that after 10?Gy hemibody irradiation, modifications persist past the acute phase. In particular, 5‐HT turnover in the distal colon is altered during a longer period.     

The value of credible data from under‐resourced areas

Data collection requires a substantial investment in human resources and infrastructure, but it is essential that it is accurate to ensure the credibility of its use. These issues are explored in the light of data from injuries in ‘disorganized’ settings based on the experiences of field hospitals staffed by the International Committee of the Red Cross. Such data was influential in the campaign to ban landmines and can be used in the legitimate questioning of states’ foreign policies. It is important to distinguish between combatant and non‐combatant weapons injuries. A significant proportion of civilian weapons injuries in combat zones, particularly post‐conflict, occur in a domestic context; some widely quoted figures for civilian war‐related injuries are too high, though the correct figures are still far too high. While reducing the supply of arms, the importance of other social factors such as education, poverty and the provision of health care is stressed ‐ provision of health care is affected in combat zones.     

Radiation‐induced fragmentation of cardiolipin in a model membrane

Purpose: To obtain evidence for the possibility of free‐radical fragmentation of cardiolipin under the action of ionizing radiation as measured by its aqueous dispersion from liposomes.

Materials and methods: Liposomes of tetramyristoylcardiolipin (TMCL) were exposed to γ‐rays from ⁶⁰Co or ¹³⁷Cs sources at doses between 1 and 24?kGy. Fragmentation products were identified using thin‐layer chromatography and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS).

Results: Using MALDI‐TOF MS and thin‐layer chromatography, it was shown that γ‐irradiation of liposomes consisting of TMCL was accompanied by free‐radical fragmentation of the lipid to form dimiristoylphosphatidic acid and dimiristoylphosphatidyl hydroxyacetone. The yields of dimiristoylphosphatidic acid were greater than those of dimiristoylphosphatidyl hydroxyacetone, and formation of the named compounds was inhibited by dissolved oxygen.

Conclusion: It is shown for the first time that on γ‐irradiation, cardiolipin can undergo free‐radical fragmentation in its polar component.     

Three‐dimensional dose distribution for partial irradiation of rat parotid glands with 200 kV X‐rays

Purpose: To investigate dose distributions in partial‐volume irradiation experiments in small experimental animals, in particular the parotid gland of rat.

Materials and methods: High‐resolution magnetic resonance imaging images were made that provided the outlines of the parotid glands, which were used to design collimators with conformal radiation ports for 100 and 50% cranial/caudal partial‐volume irradiation. A protocol for absolute dosimetry was designed and relative dose measurements were performed. From the three‐dimensional topographical data and the three‐dimensional dose distribution, dose–volume histograms were determined.

Results: The standard uncertainty of absorbed entrance dose was within 3%. Radiochromic film, thermoluminescence dosemeters and ionization chamber dose measurements revealed that the relative doses measured were in good agreement. The 20–80% penumbra of the beam across the 50% field edge was only 0.4?mm at a 6?mm depth. The gradient of the percentage depth dose from the skin of the rat to a depth of 12?mm was 1.5%?mm^?1. The absorbed doses in the cranial 50% and the caudal 50% partial volumes were comparable. This finding was reflected in the calculated dose–volume histograms of the different regions, which were similar. The dose in the shielded area between the left and right ports was about 14% of the dose near the centres of the beams.

Conclusion: The designed set‐up showed that irradiation of small volumes could be performed with high accuracy allowing the study of differences in radiation damage. Similar doses were given to the 50% cranial and 50% caudal gland volumes and, therefore, a possible difference in radiosensitivity in these volumes was not a dose effect. The approach used was also applicable for the irradiation of small volumes of other tissues.     

Molecular nature of mutations induced by irradiation with repeated low doses of X‐rays in spleen,liver, brain and testis of lacZ‐transgenic mice

Purpose: To investigate the molecular characteristics of mutations induced by repeated low doses of X‐rays in spleen, liver, brain and testis of mice.

Materials and methods: Muta^? mice, which harbour the lacZ gene contained in the lambda genome, were irradiated with 0.15?Gy every Monday, Wednesday and Friday for 6 months starting at 10 weeks of age for a total of 78 times. Four months after the last irradiation, DNAs were isolated from the four different tissues and the mutant frequencies of lacZ were determined. Next, the nucleotide sequences of the mutant lacZ genes were determined and compared with that of the wild‐type to identify the molecular changes in the mutants. The frequencies of different types of mutations were compared with those found in age‐matched non‐irradiated mice. They were also compared with those found in mice irradiated with a single high dose.

Results: The repeated low‐dose irradiation resulted in slight increases in the mutant frequency in the four kinds of tissues. The spleen, liver and brain in repeatedly irradiated mice showed higher frequencies of deletion type mutations than those of non‐irradiated mice. In testis, however, the level of the increase was modest and not statistically significant. Complex type mutations were observed only in irradiated tissues. The characteristics observed in somatic tissues were similar to those induced by a single high dose of irradiation.

Conclusions: The results suggest that the mechanism of mutation induction in vivo is similar between low‐ and high‐dose irradiation in spleen, liver and brain. The low induction of deletion mutations in testis with low‐dose irradiation suggests that spermatogonial cells have a unique DNA repair system against low‐dose radiation‐induced damage.     

IL‐1β, TNFα and IL‐6 induction in the rat brain after partial‐body irradiation: role of vagal afferents

Purpose: To evaluate the central nervous system neuroimmune and inflammatory responses during the prodromal phase of the acute irradiation syndrome in rat brains after partial‐body exposure (head‐protected) and to investigate the potential neural signalling pathways from the irradiated periphery to the non‐irradiated brain.

Material and methods: The study included four groups of rats: one irradiated group and one sham irradiated group, each containing non‐vagotomized and vagotomized rats. In vagotomized rat groups, the subdiaphragmatic vagal section surgery was carried out 45 days before the irradiation exposure. The rats were partial‐body irradiated with the head shielded with ⁶⁰Co γ‐rays to a dose of 15?Gy. They were sacrificed 6?h after the end of exposure. The hypothalamus, hippocampus, thalamus and cortex were then collected, and the concentrations of IL‐1β, TNFα and IL‐6 in each were measured by ELISA assays.

Results: Six hours after irradiation, IL‐1β levels had increased in the hypothalamus, thalamus and hippocampus, and TNFα and IL‐6 levels had increased significantly in the hypothalamus. Vagotomy before irradiation prevented these responses.

Conclusions: It was concluded that the hypothalamus, hippocampus, thalamus and cortex react rapidly to peripheral irradiation by releasing pro‐inflammatory mediators. The results also show that the vagus nerve is one of the major ascending pathways for rapid signalling to the brain with respect to partial body irradiation.